Efficacy of an Adapted Antibiotherapy in Hurley Stage 2 Hidradenitis Suppurativa Patients

Официальное название

A Multicentric Randomized Double-Blind Phase 3 Trial Evaluating the Efficacy of an Adapted Antibiotherapy in Hurley Stage 2 Active Hidradenitis Suppurativa Patients Versus Tetracycline Derivative

Обзор

The study evaluates the efficacy of an adapted antibiotherapy in Hurley stage 2 active Hidradenitis Suppurativa patients versus tetracycline derivative

Подробное описание

The antibiotic strategy is targeted against specific pathobionts which have been identified in HS lesions by the investigator's team.

Half of participants will receive a 3-week course of ceftriaxone + metronidazole treatment followed by 3 weeks of rifampicin + moxifloxacin + metronidazole combination, then 6 weeks of rifampin + moxifloxacin (experimental groupe), versus a 12 weeks course of lymecycline (control group) Double blind treatment phase will stop at week 12. All patients whatever their randomization arm or their remission status will begin follow-up treatment according to standard care recommendations (Société Française de Dermatologie): lymecycline, doxycycline or cotrimoxazole. Prescription will be upon decision of the investigator.

This maintenance treatment is not experimental.

Вмешательства

• Препарат ROCEPHIN, metronidazole, RIFADIN, IZILOX, placebo combination therapy
  a 3-week course of ceftriaxone injection + oral metronidazole followed by a 3-week course of oral rifampicin + moxifloxacin +metronidazole followed by a 6-week course of oral rifampicin + moxifloxacin
• Препарат Lymecyclin and corresponding placebos of the experimental arm
  12-week course of oral lymecycline.

Первичные конечные точки

• Percentage of patients reaching clinical remission at week 12, defined by an improvement of 90% of the IHS4 score from the baseline (IHS4 (1)) [Срок оценки: at week 12]

Вторичные конечные точки (12)

• Change in Physician Global Assessment (PGA) [Срок оценки: from baseline to week 52]
• Change in Modified Sartorius score [Срок оценки: from baseline to week 52]
• Change in Hurley Score [Срок оценки: from baseline to week 52]
• Change in Hidradenitis Suppurativa Severity Score (IHS4) score [Срок оценки: from baseline to week 52]
• Change in Hidradenitis Suppurativa Clinical Response (HiSCR) score [Срок оценки: from baseline to week 52]
• Change in Dermatology Life Quality Index (DLQI) score (Patient's HS evaluation) [Срок оценки: from baseline to week 52]
• Change of patient pain [Срок оценки: from baseline to week 52]
• Microbiological bacterial Change on the worst lesion microbiome at W12 [Срок оценки: at baseline and week 12]
• Microbiological metagenomics Change on the worst lesion microbiome at W12 [Срок оценки: at baseline and week 12]
• Number of pain killers received by patients [Срок оценки: from baseline to week 52]
• Number of antibiotic treatments received by patients [Срок оценки: from baseline to week 52]
• Time without flare of HS [Срок оценки: from baseline to week 52]

Критерии участия

Критерии включения

• Adults < 60 years old
• Diagnosis of HS according to European Dermatology guidelines:

• Recurrent inflammation occurring more than 2 times in the past 6 months in the inverse regions of the body, presenting with nodules, sinus-tracts and/or scarring.
• Signs: Involvement of axilla, genitofemoral area, perineum, gluteal area (and infra-mammary areafor women). Presence of nodules (inflamed or noninflamed), sinus tracts (inflamed or noninflamed), abscesses, scarring (atrophic, mesh-like, red, hypertrophic or linear)
• Active HS with i) ≥ 1 year of evolution and ii) ≥ 4 flares during the previous year
• Clinical severity of HS at inclusion: Hurley stage 2
• BMI < 35
• Written informed consent from patient
• Patient able to complete DLQI
• Patients affiliated to the French health system (Assurance Maladie), except French state medical aid beneficiaries (Aide Médicale d'Etat)
• Active compatible contraception for men and women of childbearing or inability to procreate
• Available laboratory blood test performed within the last 2-months

Non inclusion Criteria:

• Person < 18 and ≥ 60 years old
• Former stage 3 HS
• Previous use of the experimental treatment
• Unauthorized drugs for the study during the month preceding the inclusion
• Any contra-indication to study treatments or excipient (e.g. lactose, cornstarch, riboflavin notably):

pregnancy, breastfeeding, known allergy to experimental or reference drugs, wheat allergy, tendinopathy, QT prolongation, bradycardia, heart failure, heart rhythm disturbances, hydroelectrolytic disorders, hypokalemia, coagulation disorders, severe liver/kidney dysfunction, porphyria, mandatory use of nonsteroidal anti-inflammatory drugs (NSAIDs) for other medical conditions

• Unbalanced diabetes (ie HbA1c above 7%)
• Dysphagia, untreated gastro-oesophageal reflux/ulcer
• BMI ≥ 35
• Immune suppression, inflammatory disease, including gastroenterologic and rheumatologic inflammatory conditions
• Lactase deficiency, lactose and galactose intolerance
• Malabsorption syndrome
• Person living in the same household as another patient
• Person under guardianship or curatorship
• Individuals with any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives (e.g patient unable to complete DLQI, or poor predictable observance
• Participation in another interventional research on health products studies
• Patients requiring repeated (more than 3/year) use of antibiotics for a chronic disease other than HS
• Alcohol-dependant patients defined as an addiction to alcohol with a negative impact on health, social or personal life

Критерии исключения

Pregnancy QT prolongation Abnormal result of routine lab tests corresponding to contra-indication to study treatments Unauthorized drug for the study during all the study (from study treatments interactions listed in the SmPC, Cf. unauthorized drug listed in non-inclusion criteria).

Development of hypersensitivity to any of the study products and/or excipients (e.g. lactose, corn starch, riboflavin).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Франция · 4 центра

• Hôpital de la Timone — Marseille
• Centre Médical de l'Institut Pasteur — Paris
• Hopital St Joseph — Paris
• CHU de Rouen — Rouen

Публикации

• Guet-Revillet H, Jais JP, Ungeheuer MN, Coignard-Biehler H, Duchatelet S, Delage M, Lam T, Hovnanian A, Lortholary O, Nassif X, Nassif A, Join-Lambert O. The Microbiological Landscape of Anaerobic Infections in Hidradenitis Suppurativa: A Prospective Metagenomic Study. Clin Infect Dis. 2017 Jul 15;65(2):282-291. doi: 10.1093/cid/cix285. PMID 28379372
• Guet-Revillet H, Coignard-Biehler H, Jais JP, Quesne G, Frapy E, Poiree S, Le Guern AS, Le Fleche-Mateos A, Hovnanian A, Consigny PH, Lortholary O, Nassif X, Nassif A, Join-Lambert O. Bacterial pathogens associated with hidradenitis suppurativa, France. Emerg Infect Dis. 2014 Dec;20(12):1990-8. doi: 10.3201/eid2012.140064. PMID 25418454
• Join-Lambert O, Coignard H, Jais JP, Guet-Revillet H, Poiree S, Fraitag S, Jullien V, Ribadeau-Dumas F, Theze J, Le Guern AS, Behillil S, Lefleche A, Berche P, Consigny PH, Lortholary O, Nassif X, Nassif A. Efficacy of rifampin-moxifloxacin-metronidazole combination therapy in hidradenitis suppurativa. Dermatology. 2011 Feb;222(1):49-58. doi: 10.1159/000321716. Epub 2010 Nov 25. PMID 21109728

Идентификаторы

NCT: NCT05821478 · 2018-018

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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